Bile Acid Toxicity and Protein Kinases

2021 ◽  
pp. 229-258
Author(s):  
Atilla Engin
Keyword(s):  
Bile Acid ◽  
Protein Kinases ◽  
Acid Toxicity

scholarly journals Recent advances in understanding bile acid homeostasis

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 2029 ◽  
Author(s):  
John YL Chiang
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Farnesoid X Receptor ◽  
Recent Advances ◽  
Bile Acid Pool Size ◽  
Bile Acid Receptor ◽  
Acid Toxicity ◽  
G Protein Coupled

Bile acids are derived from cholesterol to facilitate intestinal nutrient absorption and biliary secretion of cholesterol. Recent studies have identified bile acids as signaling molecules that activate nuclear farnesoid X receptor (FXR) and membrane G protein-coupled bile acid receptor-1 (Gpbar-1, also known as TGR5) to maintain metabolic homeostasis and protect liver and other tissues and cells from bile acid toxicity. Bile acid homeostasis is regulated by a complex mechanism of feedback and feedforward regulation that is not completely understood. This review will cover recent advances in bile acid signaling and emerging concepts about the classic and alternative bile acid synthesis pathway, bile acid composition and bile acid pool size, and intestinal bile acid signaling and gut microbiome in regulation of bile acid homeostasis.

96 KNOCKOUT OF THE PSC RISK GENE FUT2 SENSITIZES MICE TO HEPATO-BILIARY BILE ACID TOXICITY

2013 ◽  
Vol 58 ◽  
pp. S42 ◽  
Author(s):  
L. Maroni ◽  
D. Tolenaars ◽  
T.H. Karlsen ◽  
R. Oude Elferink ◽  
U. Beuers
Keyword(s):  
Bile Acid ◽  
Biliary Bile Acid ◽  
Risk Gene ◽  
Acid Toxicity

Activation of LXRs prevents bile acid toxicity and cholestasis in female mice

Hepatology ◽  
2007 ◽  
Vol 45 (2) ◽  
pp. 422-432 ◽  
Author(s):  
Hirdesh Uppal ◽  
Simrat P.S. Saini ◽  
Antonio Moschetta ◽  
Ying Mu ◽  
Jie Zhou ◽  
...  
Keyword(s):  
Bile Acid ◽  
Female Mice ◽  
Acid Toxicity

scholarly journals Complementary Roles of Farnesoid X Receptor, Pregnane X Receptor, and Constitutive Androstane Receptor in Protection against Bile Acid Toxicity

2003 ◽  
Vol 278 (46) ◽  
pp. 45062-45071 ◽  
Author(s):  
Grace L. Guo ◽  
Gilles Lambert ◽  
Masahiko Negishi ◽  
Jerrold M. Ward ◽  
H. Bryan Brewer ◽  
...  
Keyword(s):  
Bile Acid ◽  
Constitutive Androstane Receptor ◽  
Pregnane X Receptor ◽  
Farnesoid X Receptor ◽  
Acid Toxicity

scholarly journals The Cholangiocyte Glycocalyx Stabilizes the ‘Biliary HCO3- Umbrella': An Integrated Line of Defense against Toxic Bile Acids

2015 ◽  
Vol 33 (3) ◽  
pp. 397-407 ◽  
Author(s):  
Lucas J. Maillette de Buy Wenniger ◽  
Simon Hohenester ◽  
Luca Maroni ◽  
Sandra J. van Vliet ◽  
Ronald P. Oude Elferink ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Protective Layer ◽  
Enzymatic Digestion ◽  
Biliary Cirrhosis ◽  
Membrane Glycoproteins ◽  
Neuraminidase Treatment ◽  
Protective Function ◽  
Membrane Bound ◽  
Acid Toxicity

Background: Destruction of cholangiocytes is the hallmark of chronic cholangiopathies such as primary biliary cirrhosis. Under physiologic conditions, cholangiocytes display a striking resistance to the high, millimolar concentrations of toxic bile salts present in bile. We recently showed that a ‘biliary HCO3- umbrella', i.e. apical cholangiocellular HCO3- secretion, prevents cholangiotoxicity of bile acids, and speculated on a role for extracellular membrane-bound glycans in the stabilization of this protective layer. This paper summarizes published and thus far unpublished evidence supporting the role of the glycocalyx in stabilizing the ‘biliary HCO3- umbrella' and thus preventing cholangiotoxicity of bile acids. Key Messages: The apical glycocalyx of a human cholangiocyte cell line and mouse liver sections were visualized by electron microscopy. FACS analysis was used to characterize the surface glycan profile of cultured human cholangiocytes. Using enzymatic digestion with neuraminidase the cholangiocyte glycocalyx was desialylated to test its protective function. Using lectin assays, we demonstrated that the main N-glycans in human and mouse cholangiocytes were sialylated biantennary structures, accompanied by high expression of the H-antigen (α1-2 fucose). Apical neuraminidase treatment induced desialylation without affecting cell viability, but lowered cholangiocellular resistance to bile acid-induced toxicity: both glycochenodeoxycholate and chenodeoxycholate (pKa ≥4), but not taurochenodeoxycholate (pKa <2), displayed cholangiotoxic effects after desialylation. A 24-hour reconstitution period allowed cholangiocytes to recover to a pretreatment bile salt susceptibility pattern. Conclusion: Experimental evidence indicates that an apical cholangiocyte glycocalyx with glycosylated mucins and other glycan-bearing membrane glycoproteins stabilizes the ‘biliary HCO3- umbrella', thus aiding in the protection of human cholangiocytes against bile acid toxicity.

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